Immuno of Lacrimal Gland and Tear Film

What are the major components of the EALT?

CALT, LGALT, LDALT

What are the major plasma cells that are present in the diffuse lymphoid effector tissue?

IgA secreting

What does EALT favor immune tolerance against?

self-antigens and nonpathogenic external antigens

What anti-inflammatory molecules does EALT use to maintain immune tolerance?

TGF-beta, IL-10, IL-1RA, sIgA, Treg cells

What does a lymphoid follicle consist of?

lymphoid B-cell follicle, para-follicular T-cell zone, DC, HEV, FAE

What is the function of microfold cells (M cells)?

transport of pathogens to DC

What is the function of lymphoid follicles?

uptake and presentation of antigens to generate effector cells

What do acinar epithelial cells secrete?

growth factor, lysozyme, lipocalin, lactoferrin

What produces the aqueous layer of the tear film?

acinar epithelial cells

What is the major lymphocyte in the lacrimal gland?

IgA secreting plasma cells

Which RNA virus is the most common cause of a virus induced lacrimal gland enlargement?

Mumps

Which DNA virus is the most common cause of a virus induced lacrimal gland enlargement?

Epstein-Barr

Which gram-positive bacteria is the most common cause of a bacteria induced lacrimal gland enlargement?

strep. pneumoniae

Which gram-negative bacteria is the most common cause of a bacteria induced lacrimal gland enlargement?

H. Influenzae

What is the cause of lacrimal gland enlargement in patients with Sjogren's syndrome?

HLA-DR3/DR4

What is the cause of lacrimal gland enlargement in patients with systemic lupus erythematosus?

HLA-DR3

What is the cause of lacrimal gland enlargement in patients with granulomatosis with polyangiitis (Wegener granulomatosis)?

GPA

What is the cause of lacrimal gland enlargement in patients with Immunoglobulin G4-related disease?

IgG4 positive plasma

Why does reactive lymphoid hyperplasia play a role in lacrimal gland enlargement?

increased number of lymphocytes in the lymphoid tissue

Which mucin is membrane-bound?

MUC1 and MUC16

Which mucin is secreted?

MUC5AC

What immune cells does the aqueous layer of the tear film contain?

lysozyme, lactoferrin, defensins, secretory IgA

What is the function of lysozyme?

breaks down bacterial peptidoglycan

What is the function of lysozyme in fungal cell walls?

cleaves chitodextrin

What is secreted by the acinar epithelium of the lacrimal gland and breaks down bacterial membranes?

SPLA2, SLPI

What component of the tear film binds to iron?

lactoferrin

What component of the tear film binds to siderophores?

lipocalin

Which components of the tear film are secreted by the lacrimal gland and function to deprive bacteria and fungi of iron?

lactoferrin and lipocalin

What is the predominant antibody in tears?

secretory IgA

Which defensins are secreted by epithelial cells, macrophages, monocytes, dendritic cells, and keratinocytes?

hBD-1, hBD-2, hBD-3

Which bacteria is LPS present in?

gram neg

Which bacteria is LTA present in?

gram pos

What is the mechanism of cathelicidin LL-37 in the tear film?

disrupts microbial membrane or viral envelope

Which layer of the tear film harbors the commensals of the ocular surface?

mucin layer

Which immune system is activated in response to an overgrowth of the ocular surface normal flora?

innate

Which cells are important innate surveillance PRR in the tear film?

C3 and SP-D

What are the components of the tear defense mechanism that predominate in opened eye conditions?

lysozyme, lactoferrin, lipocalin

What are the components of the tear defense mechanism that predominate in closed eye conditions?

Secretory IgA

Why are the classical and lectin pathways of the complement system not functioning in normal tears?

C1 stops it

Which pathway of the complement system functions in normal tears?

alternative

How does lactoferrin regulate the complement system?

prevents formation of C3 convertase

How does CD55 regulate the complement system?

inhibits C3 and C5 convertase

How does CD59 regulate the complement system?

inhibits MAC

How does C1INH regulate the complement system?

controls activation of lectin and classical pathways

How does CPN1 regulate the complement system?

inactivates C3a and C5a

Secretory IgA is a _________ IgA, whereas serum IgA is a ___________ IgA.

dimeric; monomeric

What makes it possible for N. Gonorrhea to cause corneal perforation?

it has IgA protease which breaks down IgA

The ocular surface immune system is known to promote ________________.

immune tolerance

The ocular surface microbiome is known to facilitate ________________________.

immune activation against pathogenic microbes

Which bacteria are part of the normal ocular surface microbiome?

Staph Epi, C. Acnes, C. Mastitidis

How does Corynebacterium mastitidis promote immune protection and maintains the epithelial barrier function of the ocular surface?

helps induce gamma-delta T-cells to produce IL-17 and IL-22 which increase neutrophils and tight junction expression

How is gut dysbiosis related to DED?

can cause the depletion of goblet cells which leads to less mucin

What do the probiotic properties of lactobacillus in the tear film aid in?

strengthen tight junctions, stimulate Tregs to secrete IL-10 and TGF-beta, promote IgA, AMPs, and bacteriocins

What is the role of TH1 and TH17 cells in the immunopathology of dry eyes?

retained in inflamed tissues

Which cells are secreted by TH1 cells and can induce the apoptosis of epithelial cells and the operization of ICAM I expression?

TNF-alpha

Which cells are secreted by TH1 cells and help induce the proliferation of TH1 and TH17?

IL-2

Which cells are secreted by TH1 cells and cause an increase in the expression of MCH II and ICAM I receptors and destroy goblet cells?

IFN-gamma

What is the function IL-17?

increase neutrophils and MMP expression

What is chronic inflammation in DED associated with?

reduced corneal sensation and TH1 and TH17 mediated inflammation

What causes a decrease in MUC5AC in DED?

depletion of goblet cells

How does tacrolimus work?

blocks IL-2 receptor expression and reduces IL-2 production, suppressing IL-4 and IL-5 release

What does tacrolimus inhibit?

calcineurin

What do integrin antagonists inhibit?

LFA-1

What does cyclosporine do?

decreases MHC II expression, IL-2 synthesis, and TH1, TH2 and TH17 levels

Which cytokines cause inflammation in response to mechanical irritation?

IL-1, TNF-alpha, IL-8

What is are the pathological mechanisms of MGD?

hyperkeratinization of meibomian ductal epithelium, altered lipid composition, increase bacterial colony

How does the hyperkeratinization of meibomian ductal epithelium contribute to MGD?

reduced lumen size and meibum production

Which cytokines are pro-inflammatory?

IL-1, IL-8, TNF-alpha

How do systemic tetracycline derivatives help in treating MGD?

decrease production of lipase and commensal population size